Multiplexed tumor-mimetic dECM-chip platform for colorectal cancer: Interrogating pharmacological synergy and NK cell

Yang Li1, Jia-Long Wang1, Li-Guo Liang2

  • 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Talanta
|October 25, 2025
PubMed

Insights

A novel organoid-on-a-chip platform using decellularized intestinal matrix (dECM) hydrogels enhances colorectal cancer (CRC) drug toxicity analysis and natural killer (NK) cell exosome efficacy evaluation.

Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Tissue Engineering

Background:

  • Colorectal cancer (CRC) presents significant heterogeneity and treatment challenges.
  • Existing models often fail to replicate the complex tumor microenvironment.

Purpose of the Study:

  • To develop an innovative organoid-on-a-chip platform for CRC research.
  • To assess drug toxicity and natural killer (NK) cell-derived exosome efficacy.
  • To create a more physiologically relevant model for personalized medicine.

Main Methods:

  • Fabrication of a 5% GelMA-dECM hydrogel scaffold with specific pore sizes (50-150 μm).
  • Utilizing microfluidic control to mimic dynamic physiological conditions.
  • Culturing colorectal tumor-like organoids within the 3D scaffold.
  • Comparing the efficacy of NK cell-derived exosomes in 2D versus 3D environments.

Main Results:

  • The GelMA-dECM scaffolds exhibited mechanical properties and pore structures suitable for long-term organoid culture.
  • NK cell-derived exosomes demonstrated enhanced killing effects in the 3D organoid-on-a-chip model, particularly targeting hypoxic regions.
  • The platform closely mimics the dynamic colorectal tumor microenvironment.

Conclusions:

  • The organoid-on-a-chip platform provides a superior model for evaluating CRC treatments compared to traditional 2D methods.
  • This technology can reduce the need for animal testing and advance personalized precision medicine in CRC.
  • The platform shows potential for simulating the tumor immunomicroenvironment for clinical applications.

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